1. Field of the Invention
The present invention provides a method for inhibiting osteoclast development and a method for preventing bone erosion by delivering an effective amount of a haloanilide to an osteoclast for inhibiting the osteoclast development and preventing bone erosion. Preferably, the haloanilide is N-(3,4-dibromophenyl)propanamide, N-(3,4-dichlorophenyl)-N-methylpropanamide, N-(3,4-dichlorophenyl)-N,2-dimethylpropanamide), N-(3,4-dichlorophenyl)-2-dimethylpropanamide, N-(3,4-dichlorophenyl)isobutyramide, or N-(3,4-dichlorophenyl)-N-methylisobutyramide.
2. Background Art
The composition N-(3,4-dichlorophenyl)propanamide (“DCPA”) is commercially available under the tradename “Propanil” for use as a herbicide. Its primary use in to control grassy weeds in rice fields because rice, as well as wheat, has naturally higher levels of acylamidase. Acylamidase enzymatically breaks DCPA into dichloroaniline (DCA) and water, thus inactivating the herbicide qualities of the DCPA. DCA is not toxic to plants, and the rice is unharmed but grassy weeds, which have low natural levels of acylamidase, are killed by the herbicide DCPA. Generally, the herbicide DCPA is applied numerous times during a growing season, often by spray plane because the rice is grown under very wet conditions.
The toxicity of DCPA has been investigated. It is actually of low systemic toxicity. Mice can tolerate doses in excess of 100 mg/kg and only doses >150 mg/kg produce frank immunotoxicity. The metabolism of DCPA by acylamidase produces DCA as mentioned above. DCA is then metabolized to N—OH-DCA and 6-OH-DCA. Both N—OH-DCA and 6-OH-DCA contribute to the systemic toxicity associated with in vivo administration of DCPA.
It is known that DCPA is anti-inflammatory. DCPA is capable of reducing the secretion of pro-inflammatory cytokines from macrophages both in vivo and ex vivo. The mechanism of the anti-inflammatory effect of DCPA was first determined in 1997. This mechanism is that DCPA is capable of inhibiting intracellular calcium release in macrophages.